Tularaemia
Tularaemia is a zoonosis, an infection which can be spread from animals to humans to cause an acute, febrile, granulomatous infection. It is caused by the bacterium Francisella tularensis which can infect many animals, especially small rodents, rabbits and hares. F. tularensis is very infectious and requires as few as 10 organisms to initiate human infection.2 Attempts have been made to develop tularaemia for biological warfare and these have focussed on the airborne dispersal route.
Epidemiology
· Tularemia infections occur throughout the Northern Hemisphere. There are two types of the bacterium, both of which can infect humans.
o Type A infects animals and ticks in North America. Infection is often sporadic and severe and can be fatal in humans. Type A infections have not been described as occurring naturally outside North America.
o Type B occurs in animals throughout the northern hemisphere including North America, causes milder symptoms than type A, and does not cause fatal infections. Large outbreaks have occurred.
· Type A and Type B infections can cause any of the clinical presentations listed below.
· Neither type occurs naturally within the United Kingdom.
Transmission
Person to person transmission of F. tularensis has never been documented. Infection may occur by:
· Bite of an insect, e.g. tick or mosquito, which has fed on an infected animal.
· Direct contact with the tissues/secretions of infected animals.
· Inhaling or ingesting bacteria.
· Contact with or consumption of contaminated food or water.
Presentation
There are six well-recognised clinical forms:
· Ulceroglandular tularemia:
o Approximately 80% of cases.
o Infection is usually via a scratch or abrasion which causes an ulcerated skin lesion at the site of entry and is associated with painful regional lymphadenopathy.
· Glandular tularemia:
o Similar to the ulceroglandular form except for the absence of the characteristic skin lesion.
· Oculoglandular tularemia:
o Accounts for 1-2% of patients.
o The organism enters via the conjunctivae, causing a unilateral, painful, purulent conjunctivitis with submandibular, preauricular, and cervical lymphadenopathy.
· Oropharyngeal tularemia:
o Rare form; infection occurs from eating poorly cooked meat of an infected rabbit.
o Usually presents with a sore throat (pharyngotonsillitis with regional adenopathy), abdominal pain (mesenteric lymphadenopathy), nausea, vomiting, diarrhoea and occasionally frank gastrointestinal bleeding from intestinal ulcerations.
· Pneumonic tularemia:
o Primary lung infection is rarely acquired naturally, but may develop in laboratory workers.
o However, pneumonia may develop after haematogenous spread in 10-15% of patients with ulceroglandular tularemia and in 30-80% of those with typhoidal tularemia.
o Usually presents with a dry cough, dyspnoea and pleuritic chest pain.
o Chest examination may be normal.
o Lobar pneumonia and/or adult respiratory distress syndrome may develop.
· Typhoidal (septicaemic):
o Accounts for 10-15% of tularemia cases.
o Is more severe and patients present with fever, chills, myalgia, malaise, and weight loss.
o Often have pneumonia. Ulcers and lymphadenopathy are usually absent.
· Other possible manifestations: include acute renal failure, abnormal liver function tests, and rhabdomyolysis.
· Rare manifestations include osteomyelitis, pericarditis, peritonitis, endocarditis, and meningitis.
Symptoms
Symptoms usually develop 2-5 days after infection, but the incubation period can be as short as 1 day or as long as 3 weeks. Natural infection can result in a variety of symptoms:
· Ulcers: common and occur either at the site of an infected insect bite, or sometimes on the surface of the eye following exposure to air-borne bacteria. The ulcers may be accompanied by swollen lymph nodes, general aches and fevers.
· Sore throat, pharyngitis or tonsillitis: after consumption of contaminated food or water.
· Less commonly, acute flu-like illness, often with diarrhoea and vomiting, can occur following inhalation or ingestion of the bacteria.
· Pneumonia and blood poisoning: most serious, and least common natural forms of the disease (but the most likely to occur following deliberate airborne release). Symptoms would include sudden onset of high fever, chills, muscle aches, dry cough and weakness.
Signs
· Rash: as many as 20% of patients may have a blotchy, macular, maculopapular, or pustular rash.
· Patients have fever and possibly tender hepatosplenomegaly.
· Otherwise, physical findings vary with the clinical form of disease presentation.
Differential diagnosis
· Similar bioterrorism agents such as plague, pulmonary anthrax or Q fever
· Tick-borne diseases, e.g. Colorado tick fever
· Systemic fungal infections
Investigations
· White cell count may be slightly elevated. Liver function is usually normal. An elevated creatine phosphokinase level may be associated with rhabdomyolysis and is a poor prognostic sign.
· Routine blood culture results are usually negative. Successful identification requires media containing cysteine for growth. Cultivation in the laboratory poses a hazard for laboratory staff.
· Diagnosis is usually based on serology: detection by polymerase chain reaction allows early diagnosis. Tularemia serology tests may cross-react with Salmonella, Brucella, Yersinia, and Legionella species.
· Skin testing may detect a cellular immune response and is both sensitive and specific (but skin test antigens are not commercially available).
· Biopsy of lymph nodes: usually not needed for diagnosis.
Management
· Symptomatic and supportive care for accompanying conditions (eg, osteomyelitis, pericarditis, peritonitis) as clinically indicated.
· Antibiotic eradication: recommended treatment for tularaemia is either a 10 day course of streptomycin (drug of choice) or gentamicin.
· Chloramphenicol and tetracycline are also effective but with a higher relapse rate.
· Case reports indicate a potential role for erythromycin or fluoroquinolones (ciprofloxacin, levofloxacin) but there is limited supporting evidence.
Complications
Prognosis
· If treated, the overall mortality rate of type A tularaemia is 1-3%.
· In untreated cases, the mortality rate of type A infections ranges from 4% for some of the ulcerative conditions, to 30-60% for the more serious forms of the disease.
· Mortality is 2-3 times higher in patients with the typhoidal form of the disease than in those with other forms.
Prevention
· Prevention of naturally occurring disease depends largely on:
o Avoiding tick bites: wear trousers and long-sleeved shirts, use tick repellants and frequent inspection for evidence of ticks. Remove ticks promptly but take care not to squeeze the body because tick secretions may be infectious.
o Wear gloves when exposure to dead or wild animals is necessary (eg, skinning or eviscerating a rabbit carcass).
o Wild animal meats must be cooked thoroughly before consumption.
o Frequent and thorough hand washing is also advised.
· Streptomycin, gentamicin, doxycycline or ciprofloxacin are recommended for post-exposure prophylaxis and must be taken for at least 14 days.
· A live attenuated vaccine was developed and has been used to immunise laboratory staff who work with F. tularensis. The vaccine is unlicensed and provides incomplete protection, particularly against inhaled tularaemia. It is not currently recommended for use as post-exposure prophylaxis.
Document references
2. Bossi P, Tegnell A, Baka A, et al; Bichat guidelines for the clinical management of tularaemia and bioterrorism-related tularaemia. Euro Surveill. 2004 Dec 15;9(12):E9-10. [abstract]
5. Johansson A, Forsman M, Sjostedt A; The development of tools for diagnosis of tularemia and typing of Francisella tularensis. APMIS. 2004 Nov-Dec;112(11-12):898-907. [abstract]
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